The Cell Culture Subcore will generate and maintain primary cultures and cell lines from various tissues and origins including human cancers, tumors in knockout mice, and mouse embryonic fibroblasts derived from genetically modified mice. Our mission is to generate and characterize human and mouse gastrointestinal tumor/cancer cell lines, which will be utilized for exploring the cellular and molecular mechanisms in gastrointestinal carcinogenesis. One of the major impediments in gastrointestinal cancer research has been the lack of normal epithelial cell lines derived from gastrointestinal tissues. To address this deficiency, the subcore will provide a service in developing epithelial cell lines from the different segments of the gastrointestinal tract of transgenic mice with gene deletions known to be associated with gastrointestinal tumor/cancer development. We will also generate epithelial cell lines from the different segments of human gastrointestinal tissues including pancreas, stomach and liver. Finally, the subcore is responsible for generation and maintenance of large-scale stocks of recombinant virus. The Tissue Morphology Subcore provides to the Program a comprehensive histopathology and tumor acquisition service. The mission of the core is to: 1) acquire human and gastrointestinal tumor/normal tissues (hepatocellular, pancreatic, and gastric)-fresh, snap frozen and paraffin embedded-from surgical procedures performed at Georgetown University Hospital (GUH) or from animal models generated by the animal models core (core A), respectively, and distribute these tumor and normal tissues to all four projects of the program as well as to the Cell Culture Subcore to generate cell lines; 2) maintain the tumor bank that will include the Georgetown University (GU) extensive in house collections of Gl tumors, as well as additional tissues obtained by the individual project leaders to enhance the existing GU collections (e.g. The Singapore collection of frozen and normal HCC specimens with compete clinical follow up (SingHealth HCC specimens) obtained by Dr. Byers-Project 2 and the Toronto Hospital for Sick Children's extensive collection of BWS tumors obtained by Dr. L. Mishra-Project 1); 3) provide a comprehensive tissue histological services, including state of the art tissue microarray and immunohistochemistry; and 4) provide expert assistance in conducting and interpreting experiments using specimens from human and animal subjects. Both subcores will function as a synergistic hub in the Program by working closely with each project leader as well as with the other cores (Animal Models Core-Core A and Administrative Core-Core C) to insure that the proper tissues are obtained/archived/frozen and the necessary human and mouse cell lines are generated.